In vivo models in breast cancer research: progress, challenges and future directions

Research using animal model systems has been instrumental in delivering improved therapies for breast cancer, as well as in generating new insights into the mechanisms that underpin development of the disease. A large number of different models are now available, reflecting different types and stages of the disease; choosing which one to use depends on the specific research question(s) to be investigated. Based on presentations and discussions from leading experts who attended a recent workshop focused on in vivo models of breast cancer, this article provides a perspective on the many varied uses of these models in breast cancer research, their strengths, associated challenges and future directions. Among the questions discussed were: how well do models represent the different stages of human disease; how can we model the involvement of the human immune system and microenvironment in breast cancer; what are the appropriate models of metastatic disease; can we use models to carry out preclinical drug trials and identify pathways responsible for drug resistance; and what are the limitations of patient-derived xenograft models? We briefly outline the areas where the existing breast cancer models require improvement in light of the increased understanding of the disease process, reflecting the drive towards more personalised therapies and identification of mechanisms of drug resistance

The Sharing Experimental Animal Resources, Coordinating Holdings (SEARCH) Framework : Encouraging Reduction, Replacement, and Refinement in Animal Research

National Centre for the Replacement, Refinement and Reduction of Animals in Research https://www.nc3rs.org.uk/ (grant number NC/L001004/1) received by VS. The Pathological Society of Great Britain and Ireland http://www.pathsoc.org/ (grant number OS2015 060 2) received by VS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Diagram of the SEARCH framework to connect researchers, share materials, and accelerate discovery whilst reducing animal use.

<p>Diagram of the SEARCH framework to connect researchers, share materials, and accelerate discovery whilst reducing animal use.</p

SEARCH discovery pipeline.

<p>(A) Traditional experimental workflow for in vivo research. (B) Advantages of utilising the faster and more streamlined SEARCH workflow. (C) Case study 1 showing the advantages of using models deposited in SEARCHBreast. (D) Case study 2 with an example of how SEARCH can accelerate tissue sharing and experimental discovery.</p

Summary of responses to our Bristol Online Survey.

<p>Participants were asked (A) if they used animals in research, their type (GEM, genetically engineered mouse; PDX, patient-derived xenograft), and if their work would benefit from an in vivo component; (B) if they stored surplus material; (C) if they would be willing to share this material; and (D) if they would support a SEARCH initiative.</p